In the pharmaceutical discovery process, high-throughput screening methods and systems have been touted as one method among many, for at least initially identifying promising new pharmaceutical candidate compounds. These methods and systems have been described for use in conjunction with, or even in place of more traditional rational drug design procedures and methods.
In the past, high-throughput screening operations have simply involved the incorporation of very complex automation elements, e.g., robotics and multiplexed fluid handling systems, in order to carry out assay methods developed for use with conventional technologies, but in massively parallel experiments. Specifically, large numbers of standard assays are carried out in multi-well assay plates into which reagents are dispensed using the automated and highly parallelized fluid handling systems and robotic plate handling equipment. While such systems have increased the number of different materials that can be screened, these systems tend to be extremely complex, relatively unreliable, and have large space, reagent and cost requirements for acquiring and maintaining the overall systems.
Microfluidic devices and systems have been described as potential avenues for performing these high-throughput screening operations while minimizing the space, reagent and cost requirements of the overall systems. However, such systems have largely failed in this respect due to an inability to conveniently introduce large numbers of different reagents into the microfluidic systems. Specifically, such systems have generally relied upon conventional, large expensive fluid handling systems to introduce samples and reagents into reservoirs on microfluidic devices, effectively `giving back` any cost or space advantages that would have been realized.
U.S. Pat. No. 5,779,868, and Published International Patent Application Nos. 98/00705 and 98/00231, on the other hand, describe microfluidic devices and systems for use in performing ultra high-throughput screening assays, which devices and systems incorporate an integrated sampling system, or "world to chip" interface, for accessing external materials and delivering them onto the device or LabChip.TM.. These systems typically incorporate a sampling pipettor integrated into the microfluidic system for directly accessing samples, reagents and other materials from sources of such materials, e.g., compound libraries, etc. Integrated pipettor systems have generally proven very effective in rapidly, efficiently and accurately accessing large numbers of different reagents and transporting those reagents into analytical channels.
Despite the effectiveness of these integrated pipettor systems in microfluidic applications, it would generally be desirable to provide such systems with improved structural, interfacing and flow characteristics. The present invention meets these and a variety of other needs.